Ultra Antibody Combination Inhibits COVID-19 Virus
Ultra antibody combination inhibits COVID-19 virus, animal experiments show protective effects. A few days ago, the research progress of a new coronavirus neutralizing antibody was officially published in the top academic journal Science.
An international research team composed of dozens of scientists reported on two powerful neutralizing antibodies and revealed the specific mechanisms by which they recognize and prevent viruses from infecting cells. Preclinical studies have shown that the use of these two antibodies alone or in combination can protect animals from infection by the new coronavirus. The researchers pointed out that because different antibodies use different mechanisms of action, the combined “cocktail” therapy will help combat the drug resistance of the new coronavirus due to mutations.
In this study, scientists isolated B cells from two survivors of severe COVID-19 and screened nearly 800 monoclonal antibodies that target the spike protein of the new coronavirus. Two potent neutralizing antibodies, S2E12 and S2M11, stand out. The IC50 for neutralizing live virus is as low as 0.04 nM and 0.02 nM, respectively.
▲Two neutralizing antibodies S2E12 and S2M11 targeting the spike protein of the new coronavirus (picture source: reference )
Animal challenge experiments have shown that these two antibodies can provide good protection with only a very low dose. “Among the various human monoclonal antibodies tested with the hamster model, this is the antibody with the lowest dose currently required.” The paper pointed out.
The researchers injected hamsters with S2E12, S2M11, and a mixture of two monoclonal antibodies, and exposed them to the new coronavirus 48 hours later. After 4 days, when they examined the lung tissues of the animals, they found that whether it was a single monoclonal antibody or a combination of two antibodies, the preventive injection effectively eliminated the replication of the virus in the lungs. Compared with the control group, the viral nucleic acid The number dropped by 2 to 5 orders of magnitude.
▲The results of the challenge experiment show that S2E12 and S2M11 and their “cocktail” can provide strong protection and eliminate the replication of the new coronavirus in animals (picture source: reference )
For the mechanism of action of these two powerful antibodies, the researchers also did a detailed analysis, using cryo-electron microscopy (cryo-EM) to determine their role at the molecular level. The 3D structure data showed that both S2E12 and S2M11 can recognize the receptor binding domain (RBD) of the new coronavirus spike protein, and competitively prevent the host cell ACE2 receptor from binding to RBD.
In addition to directly preventing the interaction between the virus and the receptor, S2M11 can also lock the spike protein into an inactive conformation that cannot bind to the receptor, which means that the virus will not be able to fuse with the cell membrane, making it unable to invade the cell.
▲S2M11 combines with the spike protein trimer to lock the virus in a state where it cannot bind to the receptor (picture source: reference )
Leading this research is the University of Washington and Vir Biotechnology, a company focused on developing infectious disease treatments. Not long ago, a neutralizing antibody S309 developed by this research team showed a “broad-spectrum” anti-coronavirus potential in in vitro experiments. The optimized version based on S309 has now entered clinical phase 2/3 evaluation.
The researchers pointed out in the paper that the combination of S2M11 and S2E12 or their mixture with S309 can have a synergistic effect on the neutralization efficiency. Due to the unique and complementary mechanism of action, different formulations of the antibody “cocktail” will help neutralize a variety of different virus mutants, thereby controlling the spread of the virus and reducing the problems caused by drug resistance mutations in clinical applications.
In order to determine the safety and effectiveness, the two new powerful neutralizing antibodies and their combinations reported in this study also need to be verified by subsequent human trials. We look forward to more good news from the results of clinical trials!
(Source: Reference News)